1. Field of the Invention
The invention relates to naphthalene derivatives which are useful in the treatment of certain dermatological conditions and in inhibiting lipoxygenase activity, particularly 5-lipoxygenase activity. Thus the compounds are useful both for topical treatment of inflammatory states in mammals and for systemic treatment of a variety of disease-states, including inflammation and hypersensitivity, caused by lipoxygenase activity in mammals, particularly 5-lipoxygenase activity. This invention also relates to pharmaceutical compositions useful in topically relieving the effects of certain chronic recurrent papulosquamous dermatoses, e.g., psoriasis, and in systemically relieving a variety of disease-states (including inflammatory states caused by an influx of leukocytes) caused by lipoxygenase activity, particularly 5-lipoxygenase activity. This invention also relates to a process for preparing compounds of this invention.
2. Related Disclosures
Psoriasis is a skin disease characterized in part by excessive proliferation of cells of the epidermis which remain strongly adherent and build up into a scaley plaque typical of the disease. While currently available therapies, such as corticosteroids, vitamin A derivatives (retinoids), cancer chemotherapeutic agents (methotrexate, razoxane), coal tar and anthralin preparations, and psoralen-u.v. irradiation (PUVA) are effective in controlling the disease to a certain extent, they can cause numerous and sometimes severe undesirable side effects including renal irritation, hepatic toxicity, and erythema.
Certain naphthoquinone derivatives are known to be useful in treating psoriasis. See, for example, U.S. Pat. Nos. 4,229,478, 4,466,981 and 4,593,120 and British Patent No. 1,243,401. Carbamate and carbonate derivatives of naphthalene having insecticidal properties are known. See, for example, U.S. Pat. Nos. 2,383,392, 3,958,006 and 4,181,741. Surprisingly, it has been discovered that the compounds of the instant invention are also effective antipsoriatic agents. Compounds of formula (I) provide prolonged activity in the treatment of psoriasis because of their stability upon application and slow conversion to compounds of formula (XII) and (XIII). Further, the compounds of the present invention are more stable in the topical formulations normally used.
In addition, it has been surprisingly discovered that the compounds of formula (I) are systemically effective in the inhibition of lipoxygenase activity in mammals, particularly 5-lipoxygenase activity. They are thus useful in relieving a variety of disease-states, including inflammatory states and hypersensitivity, caused by such lipoxygenase activity.